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Sophia was born on April 17, 1906 in Sicily with her brothers, Angelo and Vito and her sisters, Angela and Regina. It was revealed that her 50th birthday was in April 1956 in 1 episode (however, in the first episode of The Golden Palace (1992), it was revealed that Sophia was 87, though in several episodes, she is revealed to be between the ages of 80 and 85). In the 1987 episode, And Then There Was One, Sophia stated she has been walking since 1904. While in Sicily, as a teenager, she was briefly engaged to a man from her village, Augustine Bagatelli. Later, she became engaged to Giuseppe Mangiacavallo, who jilted her at the altar. She moved to New York after she annulled her arranged first marriage to Guido Spirelli when she was 14. She has no accent left to show that she grew up speaking the Sicilian language. Instead, she sports a thick Brooklyn accent with a fast speaking pace, which often contributed to the humor in her one-liners. Then she married Salvadore "Sal" Petrillo (played by Sid Melton), (although one episode she states she met him when she bargained with someone in a dark alley in Sicily, and another episode she says she won him in a contest in Sicily, when she stood on a rock so they were the same height) and had 3 children with him: Dorothy Zbornak, a divorced substitute teacher; Phil Petrillo, (an unseen character) a cross-dressing welder with a wife named Angela Petrillo, and several children in a trailer park in Newark, New Jersey who later died during the series, and Gloria Harker (played by Doris Belack and Dena Dietrich), who lived in California, and married into a wealthy family. However, she later lost the fortune that her husband had left her in an investment scam.

In her older years, Sophia suffered a stroke (the effects of which are said to be a partial explanation for Sophia's uncensored and brazen remarks) and was subsequently placed in Shady Pines retirement home by Dorothy. After it was damaged in a fire, Sophia moved in with Dorothy. Sophia did not have many good things to say about "the home", alluding to poor treatment by the staff many times. Dorothy often threatened to send her back there when Sophia's behavior became out of control.

While living in Miami, Sophia had many suitors, but did not date any for a substantial amount of time. She did remarry once more, though, to Max Weinstock (Jack Gilford). Max was her late husband's long-time business partner, whom Sophia had long blamed for ruining the business, although it was later revealed Sal was responsible. Sophia and Max forgave each other after the latter reveals the truth, and the two quickly became close and got married. The newlyweds realize their romance would not work out, and they part ways as friends. However, both remained legally married, as divorce would have gone against her Catholic beliefs.

Due to Sophia's Sicilian descent, there were regular hints in the series that she and her family have some mafia connections; she has made reference to several vendettas. It is even hinted that Sophia herself has done mob work; she once stated that no one in her family had "ever left a body to be found". Sophia also claimed to have been present at the St. Valentine's Day Massacre to which she then took back stating, "Oh yeah, I was at the movies that day. All day.", although in another episode, she did say she was present at a St. Valentine's Day Massacre, not the St. Valentine's Day Massacre.

Sophia believed strongly in ancient Sicilian custom and traditions, and in the power of a "Sicilian curse." The list of people she claims to have cast curses on include: Shelley Long, the Baltimore Colts, the New York Jets, Giuseppe Mangiacavallo (the boy who stood her up at the altar), and Mr. Barton (the girls' next door neighbor who expressed disdain for Italians). She has threatened to cast a curse on Dorothy (before she found that it was prohibited by another arcane custom), and on Stan Zbornak. In the final season, Sophia spent two episodes doing odd tasks in order to save Dorothy from an ancient curse from a Sicilian strega, or witch.

Sophia also appeared in one episode of Blossom, entitled I Ain't Got No Buddy, and one episode of Nurses, entitled Temporary Setbacks.

Sophia is best known for her wisecracks, put-downs and brazen remarks, often commenting on Dorothy’s lack of love life, Blanche’s promiscuity, and Rose’s stupidity. However, despite her sharp criticism of her daughter and roommates, she loves and cares for them deeply; she even sees Rose and Blanche as surrogate daughters. The other women usually seek Sophia out for advice, which Sophia is all too willing to share, usually beginning with her catchphrase, "Picture it…"

Like Rose’s tall tales, Sophia's parables often end with a moral, from which advice can be gleaned. These stories usually also involved historical figures, with Sophia claiming to have had trysts with Pablo Picasso, Sigmund Freud, and Winston Churchill, among others. She also claims to have befriended many famous people including Golda Meir, Mama Celeste, and accidentally claimed that Robert Frost was always nipping at her nose (she was confused with Jack Frost).

Members of Sophia's family who have appeared on the program include: Her sister, Angela (Nancy Walker); her brother, Angelo and her father (both roles were played by Bill Dana); her daughter, Gloria; her husband, Sal (in flashbacks and in dream sequences); and Sophia's own mother, Eleanor, (Bea Arthur in a dual role (who also didn’t have a Sicilian accent), who also appeared exclusively in flashbacks; and even Dorothy at a younger age (played by Lyn Greene).

In her younger years, Sophia apparently had always been short, with reddish-brown hair (Estelle Getty's natural color), but in one episode she says she was "a tall voluptuous blond with a butt like granite" when she was younger (though this statement was likely a by-product of her penchant for telling tall tales). During the series' run, Sophia resembled the archetypal "old lady" in looks: White-haired, small stature, wrinkles, and large-framed eyeglasses. She was shown to have a fondness for conservative, elderly clothing such as cardigans, knee-high stockings, and muumuu dresses. Sophia owned a tan bamboo handbag which became her personal trademark, as 7 carried the purse everywhere, even around the house (including the bathroom). Sophia’s sister Angela closely resembled these traits as well.

Sophia was seen knitting a bottle cover for the sherry in the episode The Operation. It turns out that once a month, Sophia and the girls from Cloud Society stake out a few benches, drink a few bottles of Sherry and discuss the shape of clouds. She remarked that she thought she saw Pat Sajak riding side-saddle on a dolphin.

Every morning, at 7 A.M, like clockwork, Sophia pees. Unfortunately she doesn't get up until it's 8 A.M.

"Not to me. It was a retirement home, and ya know what they did? They set off the fire alarm, in a retirement home. Who can rush? Half the people have walkers, the other half can't get out of their chairs. But they've got bells going off like crazy! You know what that does to hearts that only beat a few times a week? It's not pretty!" The Pilot

"I heard noise, I thought it was robbers, so I hid my jewels. Now I can’t remember where." The Pilot

"Dorothy, anger is a lot like a piece of shredded wheat caught under your dentures. If you leave it there, you get a blister, and you gotta eat Jell-O all week. If you get rid of it, the sore heals, and you feel better." Guess Who’s Coming to the Wedding?

"Picture it..." (Frequently used in various episodes as a prelude to Sophia's detailed, sometimes unbelievable stories about her life, usually in Sicily.)

"THAT’S THE GUY!" *runs towards a parking valet with a group of elderly women and beats him up* (Last line) The Chicken and the Egg